4.12 - Immune Response to Infection Flashcards
What are the steps of the immune response to infection?
- microbial detection - bacteria, fungi, protozoa, viruses, microbiota
- innate immune response - epithelia, phagocytes, NK cells, innate lymphoid cells
- adaptive immune response - lymphoid tissues, T and B lymphocytes, antibodies, cytotoxic T cells
- memory response - memory T and B cells, quick and specific response, lifelong immunity
Leukocytes and the soluble mediators they release
- antibodies - B cells
- cytokines - T cells, large granular lymphocytes, mononuclear phagocytes
- complement - mononuclear phagocytes
- inflammatory mediators - basophils, mast cells, platelets
- interferons & cytokines - tissue cells
What are the four different pathogen niches during infection?
- extracellular e.g. Staphylococcus, Streptococcus, Candida, microbiota, worms
- surface adherent e.g. enteropathogenic & enterohaemorrhagic E. coli
- intracellular vacuolar (that occupy specialised compartment in host cell e.g. modified lysosome or ER) e.g. Salmonella, Chlamydia, Legionella, Coxiella, Plasmodium
- intracellular cytosolic e.g. viruses, Listeria, Burkholderia, Mycobacterium
How does an immune response to infection start?
- tissue damage (e.g. injury / by toxins)
- molecular detection of microbes - wrong thing in the wrong place at the wrong time
- then, intercellular communication happens e.g. interleukins
- this leads to priming of the adaptive immune response
How does an immune response to infection end?
- clearing infection
- stopping inflammatory cytokine production - more production of these can lead to tissue damage
- repairing tissue damage
- remembering the infection - immune memory
What are the components of innate immunity?
- fast acting, first line of defence, germline encoded receptors
- physical barriers - skin, mucous, epithelial cells
- humoral - complement, lectins, pentraxins, antimicrobial peptides
- cellular - neutrophils, macrophages, dendritic cells, NK cells
What are the components of adaptive immunity?
- slower but long-lasting, variable receptors that mature over time (DNA recombination)
- humoral - antibodies, complement
- cellular - cytotoxic T cells, T helper cells, T regulatory cells, B lymphocytes and plasma cells
What are the differences between innate and adaptive immunity?
SPECIFICITY:
- innate - for structures shared by classes of microbes (PAMPs)
- adaptive - for structural detail of antigens, may recognise nonmicrobial antigens
NUMBER OF MICROBIAL MOLECULES RECOGNISED:
- innate - about 1000 PAMPs
- adaptive >10^7 antigens
RECEPTORS:
- innate - encoded in germline, limited diversity
- adaptive - encoded by genes produced by somatic recombination of gene segments, greater diversity
NUMBER AND TYPES OF RECEPTORS:
- innate <100 different types of invariant receptors
- adaptive - only two types of receptors (Ig and TCR), with millions of variations of each
DISTRIBUTION OF RECEPTORS:
- innate - nonclonal - identical receptors on all cells of the same lineage
- adaptive - clonal - clones of lymphocytes with distinct specificities express different receptors
What are there differences between in the innate and adaptive responses?
- timing of the response
- cell types
- receptors and ligands
- cytokines and chemokines
- molecular effector machineries
- both arms of the immune system together provide sterilising immunity and long-term memory
What happens when resting cells encounter a pathogen?
- resting cells come into contact with pathogen and recognises it through ligands or pathogen activities
- resting cell puts gene expression changes into action which means new genes expressed and translated into proteins
- these proteins include antimicrobial molecules that are directly toxic to pathogen
- proteins also include interleukins, chemokines, interferons etc and some are released from cell to communicate with neighbouring cells that haven’t encountered pathogen directly to make them ready
- these molecules also act on primary infected cell in autocrine manner, resulting in resting cell becoming activated and ready to tackle pathogen
What are some examples of molecules acting on primary infected cell and activating them?
- naive T cells that become finetuned by antigen become CD4 or CD8 cell
- macrophage that detects LPS from gram negative bacteria becomes an activated macrophage
What are the first responders to site of injury?
- neutrophils are first to respond (short-lived, 6h) followed by monocytes that differentiate to become macrophages
- naive cells become activated upon interaction with microbes
- phagocytes control infection and limit/repair tissue damage
Why is uncontrolled activity of phagocytes bad?
- in granulomas and similar situations they can release excessive cytokines
- leads to more tissue damage than controlling infection
- excessive inflammation and inappropriate adaptive immunity
- tissue damage and blocked resolution of inflammation
How do phagocytes and other immune cells identify the class of pathogen?
- bacteria - cell wall components e.g. LPS in E. coli
- fungi - beta glucans are common fungi surface molecules and receptors like dectin-1 recognise these and signal through SRC tyrosine kinases
- viruses - viral DNA/RNA in cytoplasm detected through various molecules, receptors and sensors
What type of immune response does bacteria produce?
Live E. coli elicits immune response:
- inflammatory cytokines produced (e.g. IL-1beta that causes fever)
- antimicrobial genes (directly toxic to bacteria)
- metabolic genes (help macrophage cope with demand)
- immunomodulatory genes (so adaptive immune system appropriately primed)
Dead E. coli results in no immune response
- macrophage tries to resolve inflammation
